Abstract
The translation of tumour necrosis factor alpha (TNFalpha) mRNA is regulated by the stress-activated protein kinase p38, which also controls the stability of several pro-inflammatory mRNAs. The regulation of TNFalpha gene expression in a mouse macrophage cell line RAW264.7 was re-examined using an inhibitor of stress-activated protein kinases. Stimulation of these cells with bacterial lipopolysaccharide resulted in stabilisation of TNFalpha mRNA, which was reversed by specific inhibition of p38. An adenosine/uridine-rich element from the TNFalpha 3' untranslated region conferred p38-sensitive decay in a tetracycline-regulated mRNA stability assay. Therefore the p38 pathway also controls TNFalpha mRNA turnover.
MeSH terms
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3' Untranslated Regions / genetics
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Animals
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Cell Line
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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Gene Expression Regulation / drug effects
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HeLa Cells
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Humans
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Imidazoles / pharmacology
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JNK Mitogen-Activated Protein Kinases
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Lipopolysaccharides / pharmacology
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / physiology*
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Pyridines / pharmacology
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RNA Stability / drug effects
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RNA, Messenger / drug effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism*
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Regulatory Sequences, Nucleic Acid / genetics
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Signal Transduction / drug effects
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Tetracycline / pharmacology
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Time Factors
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Tumor Necrosis Factor-alpha / drug effects
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Tumor Necrosis Factor-alpha / genetics*
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Tumor Necrosis Factor-alpha / metabolism
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p38 Mitogen-Activated Protein Kinases
Substances
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3' Untranslated Regions
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Enzyme Inhibitors
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Imidazoles
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Lipopolysaccharides
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Pyridines
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RNA, Messenger
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Tumor Necrosis Factor-alpha
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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Tetracycline
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SB 203580